线粒体占心肌细胞体积的40%，在心肌代谢和功能调节中起着至关重要的作用。通常认为，线粒体功能障碍是胰岛素抵抗的机制之一。我们前期发现，心肌胰岛素抵抗参与心衰发生和发展，且出人意料的是，抑制线粒体功能可增加心肌胰岛素敏感性，其中活性氧（ROS）在该过程中发挥重要作用，提示线粒体-ROS参与心肌胰岛素敏感性调控。但线粒体来源的ROS如何影响心肌胰岛素信号及其机制尚不清楚。本课题拟在前期发现基础上，着重研究线粒体-ROS对心肌胰岛素敏感性的影响及其机制，包括 ①在分离的心肌细胞上通过改变线粒体功能观察胰岛素敏感性的变化；②胰岛素刺激线粒体-ROS在反馈调控胰岛素敏感性中的作用及其主要分子机制；③胰岛素抵抗条件下心肌线粒体-ROS的改变及有氧运动对其是否具有改善作用，旨在明确线粒体在心肌胰岛素抵抗中的作用及其主要机制，为从改善心肌胰岛素敏感性角度防治心衰提供新线索。

Mitochondria, accounting for 40% of cardiomyocyte volume, play an essential role in myocardial metabolic and functional regulation. It has been shown that mitochondrial dysfunction is associated with insulin resistance in cardiovascular tissue and other tissues. Our previous studies have demonstrated that insulin resistance is involved in the development of heart failure, and more importantly, inhibition of mitochondrial function increases insulin sensitivity via mitochondria-derived reactive oxygen species (ROS), suggesting an involvement of mitochondria-ROS in the regulation of myocardial insulin sensitivity. However, the mechanism underlying ROS-mediated regulation of myocardial insulin sensitivity is unclear. In this study, we aim to elucidate the role of mitochondria-ROS in myocardial insulin resistance and the underlying mechanism and to provide clues for the possible therapeutic effect of increasing insulin sensitivity in the prevention of heart failure. The study includes: 1) observe how insulin sensitivity varies with the changes of mitochondrial function in isolated myocardiocytes; 2) explore the mechanism of action of insulin-mitochondria-ROS feedback in the regulation of myocardial insulin sensitivity; 3) investigate the changes of mitochondrial ROS production in the pathophysiologic condition of insulin resistance and the possible beneficial effect of aerobic exercise in the alleviation of myocardial insulin resistance via reduced mitochondria-ROS.